Kidney stone disease is a significant health problem that consumes billions of dollars annually in health care costs and lost productivity. The bulk of these stones consist primarily of calcium oxalate. The amount of calcium and oxalate in urine are thus significant risk factors for the disease. Until recently, dietary oxalate was believed to make only a minor contribution to the amount of oxalate in urine. However, using diets carefully controlled in their content of oxalate and other nutrients, we were able to show that it contributed on average half of the oxalate excreted in urine. The goal of this research project is to determine how dietary oxalate most contributes to stone risk and to design therapeutic strategies that will offset this stone risk and prevent stobe recurrence. To date, our investigations have shown that differences in the renal handling of oxalate do not contribute to renal injury or oxidative stress following transient increases in the filtered load of oxalate produced by oral oxalate loads. We did observe that the absorption of dietary oxalate does differ in individuals, particularly that occurring in the large intestine. The first aim of this project is to identify the prevalence of hyperabsorption in normal individuals and stone formers and to determine what features are associated with this hyperabsorption. The second aim is to clarify the role of the oxalate-degrading organism, Oxalobacter formigenes in large intestinal absorption. The third aim seeks to translate these findings into directed therapies that prevent stone recurrence. We will test an interactive Internet-based program that will utilize several dietary modifications to help patients modify their diet and reduce stone risk. This translation of laboratory based findings to the clinic should be adatable to reducing a number of dietary associated risk factors and in individuals with stones other than calcium oxalate. [unreadable] [unreadable] [unreadable]